Acupuncture as Add-on Therapy to SSRIs Can Improve Outcomes of Treatment for Anxious Depression: Subgroup Analysis of the AcuSDep Trial.

Purpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD). Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted. Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group. Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted. Clinical Trials Registration: ChiCTR-TRC-08000297.

Effects of decompressive craniectomy combined with edaravone on postoperative neurological functions and hemodynamics of patients with severe traumatic brain injury.

OBJECTIVES: To assess the effects of decompressive craniectomy combined with edaravone on the postoperative neurological functions and hemodynamics of patients with severe traumatic brain injury (STBI). METHODS: The subjects included totally 186 STBI patients admitted during January 2018 and January 2021. The random number table method was adopted to set an operation group (n=82) and a combined medication group (n=104) for the subjects. The changes of the clinical indicators were observed. RESULTS: Compared with the operation group, the combined medication group had higher Neurobehavioral Cognitive Status Examination score, Barthel index score, total response rate and heart rate (p<0.05). Besides, by contrast to those of the operation group, the mean arterial pressure, myocardial zymogram indicators, postoperative neurological function indicators and total incidence rate of complications of the combined medication group were reduced (p<0.05). In comparison with the operation group, the combined medication group exhibited raised ipsilateral contralateral blood velocities (p<0.05). Furthermore, the combined medication group had a better postoperative 1-year prognosis than the operation group (p<0.05). CONCLUSION: Edaravone in combination with decompressive craniectomy benefits the postoperative improvement of neurological functions of STBI patients, effectively stabilizes the hemodynamics, induces few complications and improves the prognosis.

Acupuncture Ameliorates Depression-Like Behaviors Through Modulating the Neuroinflammation Mediated by TLR4 Signaling Pathway in Rats Exposed to Chronic Restraint Stress.

Recently, emerging evidence has identified that stress-induced activation of neuroinflammation is considered to be one of the most prevalently precipitating factors in the pathogenesis of depression. Data from clinical trials and experimental findings has verified the efficacy and safety of acupuncture in the prevention and treatment of depression. However, the mechanism of the preventive effect of acupuncture for depression has not been fully elucidated. The current study aimed to investigate the preventive effect and mechanism of acupuncture through modulating the neuroinflammation mediated by toll-like receptor 4 (TLR4) signaling pathway in rats exposed to chronic restraint stress (CRS). All rats were subjected to CRS for 21 days, with the exception of rats in control group. One hour before CRS, rats in acupuncture group were exposed to acupuncture at Baihui (GV20) and Yintang (GV29). The depression-like behaviors were evaluated by body weight assessment and sucrose preference test at 0, 7, 14, and 21 days. The expression of activated microglia in hippocampus was detected by immunofluorescence. The expression of key proteins on TLR4 signaling pathway of TLR4, MyD88, TRAF6, NF-κB p65, TNF-α, and mRNA of TLR4 in the hippocampus was detected by western blot and real-time quantitative polymerase chain reaction to investigate the effect of acupuncture on stress-induced activation of neuroinflammation. The present study provided evidence that acupuncture exerted potential preventive effect that might be mediated in part by suppressing the neuroinflammation induced by TLR4 signaling pathway, which may be a promising treatment target to improve current treatments for depression.

Trust-aware conditional adversarial domain adaptation with feature norm alignment.

Adversarial learning has proven to be an effective method for capturing transferable features for unsupervised domain adaptation. However, some existing conditional adversarial domain adaptation methods assign equal importance to different samples, ignoring the fact that hard-to-transfer samples might damage the conditional adversarial adaptation procedure. Meanwhile, some methods can only roughly align marginal distributions across domains, but cannot ensure category distributions alignment, causing classifiers to make uncertain or even wrong predictions for some target data. Furthermore, we find that the feature norms of real images usually follow a complex distribution, so directly matching the mean feature norms of two domains cannot effectively reduce the statistical discrepancy of feature norms and may potentially induce feature degradation. In this paper, we develop a Trust-aware Conditional Adversarial Domain Adaptation (TCADA) method for solving the aforementioned issues. To quantify data transferability, we suggest utilizing posterior probability modeled by a Gaussian-uniform mixture, which effectively facilitates conditional domain alignment. Based on this posterior probability, a confidence-guided alignment strategy is presented to promote precise alignment of category distributions and accelerate the learning of shared features. Moreover, a novel optimal transport-based strategy is introduced to align the feature norms and facilitate shared features becoming more informative. To encourage classifiers to make more accurate predictions for target data, we also design a mixed information-guided entropy regularization term to promote deep features being away from the decision boundaries. Extensive experiments show that our method greatly improves transfer performance on various tasks.

GmUFO1 Regulates Floral Organ Number and Shape in Soybean.

The UNUSUAL FLORAL ORGANS (UFO) gene is an essential regulatory factor of class B genes and plays a vital role in the process of inflorescence primordial and flower primordial development. The role of UFO genes in soybean was investigated to better understand the development of floral organs through gene cloning, expression analysis, and gene knockout. There are two copies of UFO genes in soybean and in situ hybridization, which have demonstrated similar expression patterns of the GmUFO1 and GmUFO2 genes in the flower primordium. The phenotypic observation of GmUFO1 knockout mutant lines (Gmufo1) showed an obvious alteration in the floral organ number and shape and mosaic organ formation. By contrast, GmUFO2 knockout mutant lines (Gmufo2) showed no obvious difference in the floral organs. However, the GmUFO1 and GmUFO2 double knockout lines (Gmufo1ufo2) showed more mosaic organs than the Gmufo1 lines, in addition to the alteration in the organ number and shape. Gene expression analysis also showed differences in the expression of major ABC function genes in the knockout lines. Based on the phenotypic and expression analysis, our results suggest the major role of GmUFO1 in the regulation of flower organ formation in soybeans and that GmUFO2 does not have any direct effect but might have an interaction role with GmUFO1 in the regulation of flower development. In conclusion, the present study identified UFO genes in soybean and improved our understanding of floral development, which could be useful for flower designs in hybrid soybean breeding.

Disruption of CHORISMATE SYNTHASE1 leads to yellow-green variegation in soybean leaves.

Yellow-green variegation leaf phenotype adds more value to ornamental plants, but it is regarded as an undesirable trait in crop plants, affecting their yields. Until recently, the underlying mechanism regulating the yellow-green variegation phenotype has remained largely unexplored in soybean. In the present study, we indentified four Glycine max leaf yellow/green variegation mutants, Gmvar1, Gmvar2, Gmvar3, and Gmvar4, from artificial mutagenesis populations. Map-based cloning, together with the allelic identification test and CRISPR-based gene knockout, proved that mutated GmCS1 controls yellow-green variegation phenotype of the Gmvar mutants. GmCS1 encodes a chorismate synthase in soybean. The content of Phe, Tyr, and Trp were dramatically decreased in Gmcs1 mutants. Exogenous supply of three aromatic amino acid mixtures, or only Phe to Gmvar mutants, leads to recovery of the mutant phenotype. The various biological processes and signalling pathways related to metabolism and biosynthesis were altered in Gmvar mutants. Collectively, our findings provide new insights about the molecular regulatory network of yellow-green variegation leaf phenotype in soybean.

Effects of acupuncture on regulating the hippocampal inflammatory response in rats exposed to post-traumatic stress disorder.

Data from clinical and experimental studies have verified the efficacy and safety of acupuncture in the treatment of post-traumatic stress disorder (PTSD). However, the concrete mechanism has not been well elucidated. The stress-induced activation of inflammatory response is involved in the development and pathogenesis of PTSD. Here, we aimed to investigate the effects of acupuncture on regulating the hippocampal inflammatory response in rats exposed to PTSD. Forty male rats were randomly divided into control, model, acupuncture and sertraline group. Within 1 day after adaptive feeding, all rats were exposed to single prolonged stress (SPS), except for the rats in the control group. Rats in acupuncture group were exposed to acupuncture intervention at the acupoints of Baihui (GV20) and Yintang (GV29), 20 min once per day for 15 days. Rats in sertraline group were exposed to a suspension of sertraline and distilled water (0.2 mg/ml), once per day for 15 days continuously. Body weight and elevated plus maze experiment were detected at different time-points to evaluate the behavioral changes of rats. HE staining method was used to observe the basic pathological morphological changes in hippocampus. Immunofluorescence staining method was used to observe the activation of hippocampal microglia. The content of IL-6 and IL-1ß in serum were detected by ELISA method. Compared with the control group, the body weight of rats in model group significantly decreased on 8 days, and the percentage of time in open arms and open arm entries decreased significantly on 15 days after SPS procedures, which indicated that SPS induced PTSD-like behavior in rats. Acupuncture exerted therapeutic effect. Simultaneously, the result of HE staining confirmed that SPS induced hippocampal morphological changes in SPS rats. Notably, acupuncture reversed the reduction and pathological injury to some extent. The results have also shown that acupuncture intervention effectively reversed the activated microglia of the hippocampus in rats. Moreover, the expression of IL-1ß in serum was significantly decreased by acupuncture intervention. In summary, the present study demonstrated that the role of acupuncture in eliminating PTSD-like behavior might be connected with reversing the pathological process of the inflammatory response mediated by the activation of microglia induced by SPS.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

ESMOLOL PROTECTS AGAINST LPS-INDUCED CARDIAC INJURY VIA THE AMPK/mTOR/ULK1 PATHWAY IN RAT.

ABSTRACT: Aim: The purpose of this study was to investigate the effect of esmolol (ES) on LPS-induced cardiac injury and the possible mechanism. Methods: Sepsis was induced by i.p. injection of LPS (10 mg/kg) in male Sprague-Dawley rats pretreated with ES, 3-methyladenine or rapamycin. The severity of myocardial damage was analyzed by hematoxylin-eosin staining, and myocardial damage scores were calculated. The concentration of cardiac troponin was measured by enzyme-linked immunosorbent assay. The expression of autophagy-related proteins (beclin-1, LC3-II, p-AMPK, p-ULK1, p-mTOR) in myocardial tissue was detected by Western blotting. Autophagosome formation and the ultrastructural damage of mitochondria were assessed using transmission electron microscopy. Results: LPS induced an increase in myocardial damage score in a time-dependent manner, accompanied with an increase in autophagy at 3 h and decrease in autophagy at 6, 12, and 24 h. Pretreatment of LPS-treated rats with ES or rapamycin reduced myocardial injury (release of cardiac troponin, myocardial damage score) and increased autophagy (LC3-II, beclin-1, p-AMPK, and p-ULK1 levels and autophagosome numbers) at 12 and 24 h. In contrast, 3-methyladenine showed no effect. Conclusion: Esmolol alleviates LPS-induced myocardial damage through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy.

Soybean GmHY2a encodes a phytochromobilin synthase that regulates internode length and flowering time.

Plant height and flowering time are important agronomic traits that directly affect soybean [Glycine max (L.) Merr.] adaptability and yield. Here, the Glycine max long internode 1 (Gmlin1) mutant was selected from an ethyl methyl sulfonate (EMS)-mutated Williams 82 population due to its long internodes and early flowering. Using bulked segregant analysis (BSA), the Gmlin1 locus was mapped to Glyma.02G304700, a homologue of the Arabidopsis HY2 gene, which encodes a phytochromobilin (PΦB) synthase involved in phytochrome chromophore synthesis. Mutation of GmHY2a results in failure of the de-etiolation response under both red and far-red light. The Gmlin1 mutant exhibits a constitutive shade avoidance response under normal light, and the mutations influence the auxin and gibberellin pathways to promote internode elongation. The Gmlin1 mutant also exhibits decreased photoperiod sensitivity. In addition, the soybean photoperiod repressor gene E1 is down-regulated in the Gmlin1 mutant, resulting in accelerated flowering. The nuclear import of phytochrome A (GmphyA) and GmphyB following light treatment is decreased in Gmlin1 protoplasts, indicating that the weak light response of the Gmlin1 mutant is caused by a decrease in functional phytochrome. Together, these results indicate that GmHY2a plays an important role in soybean phytochrome biosynthesis and provide insights into the adaptability of the soybean plant.

Genetic Mapping of the Gmpgl3 Mutant Reveals the Function of GmTic110a in Soybean Chloroplast Development.

The generation of oxygen and organic matter in plants mainly depends on photosynthesis, which directly affects plant growth and development. The chloroplast is the main organelle in which photosynthesis occurs. In this study, a Glycine max pale green leaf 3-1 (Gmpgl3-1) mutant was isolated from the soybean mutagenized population. The Gmpgl3-1 mutant presented with decreased chlorophyll contents, reduced chloroplast stroma thylakoids, reduced yields, and decreased numbers of pods per plant. Bulked segregant analysis (BSA) together with map-based cloning revealed a single-nucleotide non-synonymous mutation at the 341st nucleotide of the first exon of the chloroplast development-related GmTic110a gene. The phenotype of the knockout plants was the same as that of the mutant. The GmTic110a gene was highly expressed in the leaves at various developmental stages, and its protein was localized to the inner chloroplast membrane. Split luciferase complementation assays and coimmunoprecipitation (co-IP) experiments revealed that GmTic110a interacted with GmTic20, GmTic40a, and GmTic40b in tobacco leaves. These results indicated that the GmTic110a gene plays an important role in chloroplast development.

Transcutaneous Electrical Cranial-Auricular Acupoint Stimulation vs. Escitalopram for Patients With Mild-to-Moderate Depression (TECAS): Study Design for a Randomized Controlled, Non-inferiority Trial.

Background: Previous studies in animals and humans indicated that transcutaneous vagus nerve stimulation (tVNS) and transcutaneous electrical acupoint stimulation (TEAS) on trigeminal nerve-innervated forehead acupoints can relief the symptoms of depression. However, due to the limited investigations on these two interventions, more research are needed to confirm their efficacy in depression. To improve the efficacy of the single treatment, we combined two treatments and created a novel non-invasive stimulation, transcutaneous electrical cranial-auricular acupoint stimulation (TECAS). To assess the efficacy and safety of TECAS, we compare it with a selective serotonin reuptake inhibitor (SSRI), escitalopram, for the treatment of depression. Methods/Design: This is a multi-center, non-inferiority, randomized controlled trial that will involve 470 patients with mild to moderate depression. Patients will be randomly assigned to either the TECAS group or the escitalopram group in a 1:1 ratio. The TEAS group will receive two sessions of treatments per day for 8 consecutive weeks, and the escitalopram group will receive 8 weeks of oral escitalopram tablets prescribed by clinical psychiatrists as appropriate for their condition. The primary outcome is the clinical response as determined by Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week 8, with -10% as the non-inferior margin. The secondary outcomes include the response rate determined by 17-item Hamilton Depression Rating Scale (HAMD-17), remission rate, changes from baseline in the scores on the MADRS, the HAMD-17, the Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Short Form 36 Health Survey (SF-36). Discussion: This will be the first randomized controlled trial to compare the efficacy of TECAS with escitalopram for depression. If effective, this novel intervention could have significant clinical and research implications for patients with depression. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03909217].

Serum NLRP3 Inflammasome and BDNF: Potential Biomarkers Differentiating Reactive and Endogenous Depression.

Background: The highly heterogeneous pathogenesis of depression and limited response to current antidepressants call for more objective evidence for depression subtypes. Reactive and endogenous depression are two etiologically distinct subtypes associated with different treatment responses. This study aims to explore the potential biomarkers that differentiate reactive and endogenous depressions. Methods: The clinical manifestations and biological indicators of 64 unmedicated mild-to-moderate depression patients (32 reactive depression patients and 32 endogenous depression patients) and 21 healthy subjects were observed. The 24-item Hamilton rating scale for depression (HAMD-24) was used to evaluate the severity of depression. Serum levels of depression-related biological indicators were measured by using the enzyme-linked immunosorbent assay. Results: The NLRP3 level of reactive depression was significantly lower than those of endogenous depression and healthy controls. There was a significant negative correlation between the BDNF level and the HAMD-24 total scores for patients with reactive depression. Conclusion: Our findings suggested the serum NLRP3 and BDNF levels could be potential biomarkers for detecting and evaluating the severity of reactive depression.

Factors influencing postembolization syndrome in patients with hepatocellular carcinoma undergoing first transcatheter arterial chemoembolization.

CONTEXT: Postembolization syndrome (PES) is the most common complication in patients with hepatocellular carcinoma (HCC) who had undergone transcatheter arterial chemoembolization (TACE). PES was defined as fever, nausea and/or vomiting, and abdominal pain and these symptoms develop within 1-3 days after TACE. However, few studies have explored the factors influencing PES in patients with TACE for the first time. AIMS: We explored the factors influencing PES in patients with HCC undergoing TACE for the first time. SETTINGS AND DESIGN: The present study was a hospital-based study conducted in the tertiary care hospital of Guangzhou with a retrospective study design. SUBJECTS AND METHODS: In this single-center retrospective study, a total of 242 patients with HCC were included in the first TACE program between November 1, 2018 and November 31, 2019. STATISTICAL ANALYSIS USED: T-test and Chi-square test revealed the factors affecting the occurrence of PES. Correlation analysis (Spearman) explored the relationship between these factors and PES. Binary logistics analyzed the predictive factors of PES. RESULTS: The probability of PES in patients with HCC undergoing TACE for the first time was 55.45%. Types of embolic agents (r = 0.296), types of microspheres (r = 0.510), number of microspheres (r = 0.130), maximum diameter of microspheres used (r = 0.429), type of drug (r = 0.406), and drug loading (r = 0.433) were positively correlated with PES (P < 0.05). Serum albumin was negatively correlated with PES (P = 0.008, r = -0.170). Binary logistic regression analysis revealed that drug loading microspheres (odds ratio [OR] = 0.075, 95% confidence interval [CI] = 0.031-0.180) and serum albumin (OR = 0.182, 95% CI = 0.068-0.487) were the protective factors influencing PES, while drug loading was the risk factor of PES (OR = 1.407, 95% CI = 1.144-1.173). CONCLUSIONS: Drug loading microspheres, serum albumin, and drug loading were the predictors of PES after the first TACE.

Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction.

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.

Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer's Disease.

Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer's disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aß25-35 served as an in vitro model of Alzheimer's disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml-200 µg/ml, followed by co-incubation with 20 µM Aß25-35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aß-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aß-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aß exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.

CircRNA expression profiling and bioinformatics analysis indicate the potential biological role and clinical significance of circRNA in influenza A virus-induced lung injury.

Circular RNA (circRNA) plays an important role in the regulation of multiple biological processes. However, circRNA profiling and the potential biological role of circRNA in influenza A virus (IAV)-induced lung injury have not been investigated. In the present study, circRNA expression profiles in lung tissues from mice with and without IAV-induced lung injury were analyzed using high-throughput sequencing, and differentially expressed circRNAs were verified by quantitative PCR. The gene homology of candidate circRNAs was investigated and the expression of plasma circRNAs from patients with IAV-induced acute respiratory distress syndrome (ARDS) was detected. The target microRNAs (miRNAs) of circRNAs were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. In total, 781 circRNAs were differentially expressed between ARDS mice and control (467 were up-regulated and 314 were down-regulated). Moreover, the candidate circRNAs (Slco3a1, Nfatc2, Wdr33, and Dmd) expression showed the same trend with the sequencing results. The isoforms of circRNA Slco3a1 and Wdr33 were highly conserved between humans and mice. Plasma circRNA Slco3a1 and Wdr33 presented differential expression in patients with IAV-induced ARDS compared to control. The circRNAmiRNA interaction network and GO and KEGG analyses indicated the potential biological role of circRNAs in the development of IAV-induced lung injury. Taken together, a large number of differentially expressed circRNAs were identified in our study. CircRNA Slco3a1 and Wdr33 had significantly different expression in specimens from mice and humans, and showed a potential biological role in IAV-induced lung injury by bioinformatics analysis.

Jie-Yu Pill, A Proprietary Herbal Medicine, Ameliorates Mood Disorder-Like Behavior and Cognitive Impairment in Estrogen-Deprived Mice Exposed to Chronic Unpredictable Mild Stress: Implication for a Potential Therapy of Menopause Syndrome.

Jie-Yu Pill (JYP) is a proprietary herbal medicine initially developed to treat menstrual mood disorders. This study sought to determine whether JYP could alleviate menopausal psychiatric symptoms in ovariectomized (OVX) mice, an animal model of estrogen deprivation, exposed to chronic unpredictable mild stress (CUMS) and the underlying mechanisms in comparison with estrogen therapy. The OVX+CUMS mice were treated with 0.3 mg/kg estradiol (E2), 2.5 g/kg or 5 g/kg JYP for 36 days, and tested in multiple behavioral paradigms. Serum, uterus, and brain tissues were collected for the measurement of hypothalamus-pituitary-ovarian axis (HPO) and hypothalamus-pituitary-adrenal (HPA) axis hormones, γ-aminobutyric acid (GABA), glutamate, neurotrophins, and estrogen receptors. JYP and E2 had comparable efficacy in reducing anxiety- and depression-like behavior and cognitive impairment of the OVX+CUMS mice. E2 strikingly increased ratio of uterus to body weight of the OVX+CUMS mice, but JYP did not. Both agents suppressed HPO-axis upstream hormones, inhibited HPA-axis hyperactivity by reinstating hypothalamic GABA, restored hippocampal and prefrontal glutamate contents and its receptor expression in the OVX+CUMS mice. While JYP and E2 protected against decreases in hippocampal and prefrontal neurotrophins and estrogen receptors of the OVX+CUMS mice, unlike E2, JYP had no significant effects on these biomarkers in the uterus. These results suggest that JYP has comparable efficacy in ameliorating mood disorder-like behavior and cognitive impairment induced by a combination of estrogen deprivation and chronic stress in association with certain differential uterus-brain mechanisms compared to estrogen therapy. JYP may be a potential therapy for menopause-associated psychiatric disorders.

Subthreshold depression may exist on a spectrum with major depressive disorder: Evidence from gray matter volume and morphological brain network.

BACKGROUND: Subthreshold depression (StD) is a prevalent condition that may increase the risk of incident major depressive disorder (MDD). However, the relationship between StD and MDD remains unclear. METHODS: A total of 153 adult subjects, including 53 drug-naive MDD, 50 StD and 50 healthy control (HC) subjects, underwent a T1-weighted magnetic resonance imaging scan, and the gray matter volume (GMV) alterations among the three groups were quantitatively analyzed using voxel-based morphometry (VBM). Then, to capture the whole-brain connectivity characteristics, we constructed morphological brain networks (MBN) based on the similarity among brain regions of individual VBM images and compared the network connection strengths among the three groups. RESULTS: The StD and MDD subjects had similar patterns of GMV reductions in the orbitofrontal cortex and left temporal gyrus, although the magnitude of the reductions was smaller in StD subjects. Moreover, a total of 21 morphological connections were significantly different among the three groups. For the majority of the different connections (15/21), the connection strength of the StD group took an intermediate position between that of the MDD and HC groups. LIMITATIONS: There is still a lack of a consistent definition of StD, and the age range of the subjects in this study was wide. Meanwhile the mechanisms and biological significance of the MBN remains to be clarified. CONCLUSIONS: These results may support the hypothesis that depression is better expressed as a spectrum and that StD exists on a spectrum with MDD.